Lymphokines are soluble mediators of the cell mediated immune system and are thought to play a role in resistance to neoplastic disease. Two well characterized lymphokines, migration inhibition Factor (MIF) and interferon, appear in the sera of mice which have been sensitized to Mycobacterium bovis, strain BCG, and then challenged with specific mycobacterial antigens (old tuberculin). When this lymphokine-containing serum is injected into transplantable murine tumors it markedly inhibits the growth of those tumors. This is an especially good mode to evaluate the possible role of MIF in tumor inhibition since it appears in much higher titers than in any other system. Using this model it will be possible to quantitatively measure the concentration of MIF and determine if its activity parallels the tumor inhibiting activity of the serum. Interferon will be similarly examined. Purification techniques including salt precipitation, column chromatography and isoelectric focusing will be used to attempt to enrich the factor(s) causing tumor regression and to determine if MIF and interferon activities are separable from the tumor inhibiting activity. Studies will be made to determine physical-chemical characteristics ot the tumor inhibitor such as molecular weight, heat stability and sensitivity to enzyme digestion. The mechanism of tumor rejection will be examined. Histologic studies will describe cells present at the tumor site. Inhibitors of lymphocyte and macrophage function will define cell populations required for tumor rejection. In vitro examination of the host's immune system is involved in the tumor rejection. It is hoped that these studies will help define the role these two lymphokine mediators play in tumor resistance.